The Buspirone-dependent Abdominal Pain Transmission Within the Nucleus Tractus Solitarius in the Rat

Opposing effects of 5‐HT1A receptor agonist buspirone on supraspinal abdominal pain transmission in normal and visceral hypersensitive rats

“…The buspirone‐produced reduction in the CRD‐evoked excitation of the CVLM neurons and blood pressure response to CRD that we observed in healthy control animals is in accordance with our previous findings, demonstrating similar manifestations of visceral antinociceptive properties of the drug in normal conditions (Panteleev et al, 2018, 2021). In turn, the suppressive action of the compound on the visceromotor reactions to CRD, we showed in the control rats, is in agreement with our previous study in dogs (Lyubashina et al, 2017) and other studies reporting analgesic effect of buspirone and another 5‐HT1A agonist, 8‐OH‐DPAT in conscious animals (Abdel Salam & Baiuomy, 2007; Danzebrink & Gebhart, 1991; Galeotti et al, 1997; Korzeniewska‐Rybicka & Płaźnik, 2001; Rouzade et al, 1998; Sivarao et al, 2004).…”

“…At the same time, the linear dose‐dependent increase in the buspirone‐induced inhibition of CRD‐excited CVLM neurons, that we observed, can indicate that this effect occurred due to activation of 5‐HT1A heteroreceptors rather than autoreceptors, because the latter are known to be preferentially stimulated by low doses of the compound and mediate its pronociceptive effects (Haleem, 2019; Haleem et al, 2018). In this connection, a contribution can be made by the inhibitory action of buspirone on the 5‐HT1A‐dependent visceral nociceptive neurotransmission in the nucleus tractus solitarius that we demonstrated previously (Panteleev et al, 2021), being in agreement with the suppressive effect of 8‐OH‐DPAT on the local glutamatergic signaling within the structure reported by other authors (Ostrowski et al, 2014). A secondary result of such inhibition can be a decline in this nucleus‐induced facilitation of the CVLM visceral nociceptive neurons (Aicher et al, 1995; Nosjean et al, 2002).…”

“…In particular, 5‐HT1A agonists have been shown to produce antinociceptive effects in various visceral pain models in rodents (Abdel Salam & Baiuomy, 2007; Danzebrink & Gebhart, 1991; Galeotti et al, 1997; Korzeniewska‐Rybicka & Płaźnik, 2001; Rouzade et al, 1998; Sivarao et al, 2004). In line with these findings, we previously demonstrated that buspirone, a partial agonist of 5‐HT1A receptors, dose dependently inhibited visceromotor reactions and medullary neuronal responses to noxious colorectal distension in healthy awake dogs and anesthetized rats (Lyubashina et al, 2017; Panteleev et al, 2018, 2021). However, in other studies 5‐HT1A receptor activation led to pronociceptive effect (Coelho et al, 2001; Mickle et al, 2012), whereas 5‐HT1A antagonists attenuated visceral pain perception (Coelho et al, 1998; Lindström et al, 2009).…”

“…The observed changes in the medullary neuronal activity may equally be an immediate consequence of buspirone‐induced suppression of the CVLM nociceptive cells or a secondary result of its action on other brain and spinal sites. Considering our previous findings that visceral pain‐related effects of the compound within the caudal medulla are largely mediated by supraspinal 5‐HT1A‐dependent mechanisms (Panteleev et al, 2018, 2021), a site for such modulation is assumed to be immediately within the CVLM, where the 5‐HT1A receptors have been localized (Helke et al, 1997; Liu & Wong‐Riley, 2010; Pazos & Palacios, 1985). It seems reasonable to assume that their activation by buspirone can lead to a reduction in the excitatory serotonergic and glutamatergic neurotransmissions operating in the region (Fonseca et al, 2001; Izzo et al, 1993; Li et al, 2020; Steinbusch, 1981; Suzuki et al, 1997).…”

Supraspinal neuronal alterations promoting intestinal hyperalgesia in colitis

“…В свою очередь, полученные нами нейрофизиологические данные о существовании в висцеросенсорных областях продолговатого мозга групп нейронов, различающихся по характеру ответа на болевое колоректальное растяжение, согласуются с результатами других исследований, продемонстрировавших такие же популяции нервных клеток в каудальной ВЛРО (Lyubashina Нейрональные перестройки на супраспинальном уровне... et al 2016;Ness et al 1998;Pinto-Ribeiro et al 2011) и ЯОТ (Liu et al 2014;Panteleev et al 2021). Однако мы впервые обнаружили сходные по реакциям на висцеральную боль группы нейронов в ЦСВ среднего мозга и показали, что при кишечном воспалении соотношение и функциональные характеристики таких нейрональных групп не только в бульбарных структурах, но и на среднемозговом уровне претерпевают существенные изменения.…”